LPA is a phospholipid, for example, as represented by the following chemical formula, which has a simple structure containing a glycerol unit in which a fatty acid is present at the 1-position or 2-position and a phosphate group is bonded at, the 3-position. Examples thereof include 1-acyl LPA, 1-alkyl LPA, 1-alkenyl LPA, 2-acyl LPA, and the like. Further, it has diversity depending on the type of the fatty acid, and may be classified into 18:1-LPA, 18:3-LPA, 16:0-LPA, and the like according to the length of the carbon chain and the degree of unsaturation.

It is known that LPA is produced in various parts of the living body, both inside and outside of the cells, transduces signals into the cell mainly by binding to a G-protein coupled receptor present on the cell surface, and shows various physiological effects. 5 subtypes of LPA receptors are known, LPA1 to LPA5. Among these, three types of receptors, LPA1, LPA2, and LPA3 are also called EDG (Endothelial Differentiation Gene) 2, EDG4, and EDG7, respectively. The LPA receptors subtypes are distributed in various parts in the living body, but the localization tissue varies depending on the subtype, and it is thought that each receptor subtypes are involved in the biological functions of each tissue.
It has been reported that LPA is present in the semen in the lower urinary tract tissue (Non-Patent Document 1), and it has been revealed that LPA induces contraction of isolated urethral and prostate tissue strips in vitro, and increases the urethral pressure in vivo (Patent Document 1).
Furthermore, it has been reported that LPA induces contraction of isolated bladder smooth muscle cells, and LPA also promotes the proliferation of prostate cells obtained from benign prostatic hyperplasia (Non-Patent Documents 2 and 3).
In the nerve cells, LPA1 is highly expressed in oligodendrocytes and Schwann cells in a myelination period, and is expressed in correspondence with the period of myelination (Non-Patent Document 4).
It is also known that in a mouse model with demyelination, the amount of mRNA of LPA1 decreases by about 40% (Non-Patent Document 5).
It has been suggested that LPA inhibits the cell death of Schwann cells and oligodendrocytes, and is involved in the myelination (Non-Patent Document 6).
It has further been reported that LPA and LPA1 are involved in the expression of neuropathic pain (Non-Patent Document 7).
It has been shown that LPA is involved in various fibrotic diseases. It has been reported that in hepatic fibrosis, LPA promotes the contraction and proliferation of stellate cells which play an important role in the process of hepatic fibrosis and that the LPA concentration increases in patients with chronic hepatitis C and animal models with various hepatic diseases (Non-Patent Documents 8, 9, 10, and 11). It has further been reported that in renal fibrosis, the production of LPA and the expression of LPA1 increase in a mice with unilateral ureteral ligation model, which is an animal model of renal fibrosis, and the progression of fibrosis decreases in LPA1-deficient mice and LPA receptor antagonists (Non-Patent Document 12). It has been reported that with respect to pulmonary fibrosis, the LPA concentration in the bronchoalveolar lavage fluid in patients with idiopathic pulmonary fibrosis increases, that the LPA concentration in the bronchoalveolar lavage fluid increases in model mice with bleomycin-induced lung fibrosis, and that the progression of fibrosis and the death are remarkably inhibited in LPA1-deficient mice (Non-Patent Document 13).
In addition, it has been reported that LPA is accumulated to mediate the activation of platelets and endothelial cells by oxidized LDL in atherosclerosis lesions, and it has been suggested that LPA is involved in cardiovascular diseases (Non-Patent Document 14).
Furthermore, it is known that in the proliferative diseases, LPA promotes the migration of cancer cells (Non-Patent Document 15). It has been reported that the LPA concentration increases in the ascites of patients with ovarian cancer, and actually promotes the proliferation of the ovarian cancer cells (Non-Patent Documents 16 and 17). It has been reported that in prostate cancer, the expression of LPA1 receptor increases in the tumorlesion and the proliferation is enhanced in the prostate cancer cells overexpressing LPA1 (Non-Patent Document 18). It also has been reported that in breast cancer bone metastasis models, overexpression of LPA1 increases tumor proliferation/metastasi and LPA receptor antagonist inhibits the metastasis (Non-Patent Document 19). Further, in recent years, it has been rapidly revealed that various cells surrounding cancer cells assist the survival, growth, and distant metastasis of cancer cells in the cancer tissues. It has been revealed that human fat-derived mesenchymal stem cells differentiate into tumor-associated fibroblasts through the activation of LPA1 in tumor tissues by transplantation with cancer cells, thereby promoting the growth/angiogenesis of tumors (Non-Patent Document 20).
From the findings obtained by various studies on the LPA and LPA receptors, it is thought that an agent which inhibits the physiological activity of LPA, in particular, an antagonist of LPA1, may be useful as a drug for preventing or treating urologic diseases such as urinary disfunction associated with benign prostatic hyperplasia and the like, central/peripheral nervous system neurological diseases and uriological nerve diseases, hepatitis and renal insufficiency, fibrotic diseases such as idiopathic pulmonary fibrosis and the like, cardiovascular diseases such as atherosclerosis and the like, and proliferative diseases such as prostate cancer, breast cancer, ovarian cancer, and the like.
Meanwhile, it is known that a carboxylic acid derivative represented by the formula (A) has an LPA receptor antagonistic action and is useful for various diseases, for example, urinary system diseases, cancer-related diseases, proliferative diseases, inflammatory immune disease, brain-related diseases, chronic diseases, and the like (Patent Document 2).

(wherein Z represents an acidic group, for the others, refer to the publication.)
It is further known that a compound represented by the formula (B) has an LPA receptor antagonistic action and is useful for various diseases, for example, urinary system diseases (symptoms associated with benign prostatic hyperplasia, neurogenic bladder diseases, and the like), cancer-related diseases, proliferative diseases, inflammatory immune diseases, brain-related diseases, chronic diseases, and the like (Patent Document 3).

(for the symbols in the formula, refer to the publication.)
In any of the documents above, there is no specific disclosure of the compound of the present invention.